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  • 1
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    Global identification of transcriptional regulators of pluripotency and differentiation in embryonic stem cells (2012)
    Oxford University Press
    Details
    Publication Date: 2012-09-27
    Description: Human embryonic stem cells (hESCs) hold great promise for regenerative medicine because they can undergo unlimited self-renewal and retain the capability to differentiate into all cell types in the body. Although numerous genes/proteins such as Oct4 and Gata6 have been identified to play critical regulatory roles in self-renewal and differentiation of hESC, the majority of the regulators in these cellular processes and more importantly how these regulators co-operate with each other and/or with epigenetic modifications are still largely unknown. We propose here a systematic approach to integrate genomic and epigenomic data for identification of direct regulatory interactions. This approach allows reconstruction of cell-type-specific transcription networks in embryonic stem cells (ESCs) and fibroblasts at an unprecedented scale. Many links in the reconstructed networks coincide with known regulatory interactions or literature evidence. Systems-level analyses of these networks not only uncover novel regulators for pluripotency and differentiation, but also reveal extensive interplays between transcription factor binding and epigenetic modifications. Especially, we observed poised enhancers characterized by both active (H3K4me1) and repressive (H3K27me3) histone marks that contain enriched Oct4- and Suz12-binding sites. The success of such a systems biology approach is further supported by experimental validation of the predicted interactions.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    AntigenMap 3D: an online antigenic cartography resource (2012)
    Oxford University Press
    Details
    Publication Date: 2012-04-28
    Description: : Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. Availability and implementation: http://sysbio.cvm.msstate.edu/AntigenMap3D Contact: wan@cvm.msstate.edu ; wanhenry@yahoo.com
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 3
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    RhesusBase: a knowledgebase for the monkey research community (2012)
    Oxford University Press
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    Publication Date: 2012-12-20
    Description: Although the rhesus macaque is a unique model for the translational study of human diseases, currently its use in biomedical research is still in its infant stage due to error-prone gene structures and limited annotations. Here, we present RhesusBase for the monkey research community ( http://www.rhesusbase.org ). We performed strand-specific RNA-Seq studies in 10 macaque tissues and generated 1.2 billion 90-bp paired-end reads, covering 〉97.4% of the putative exon in macaque transcripts annotated by Ensembl. We found that at least 28.7% of the macaque transcripts were previously mis-annotated, mainly due to incorrect exon–intron boundaries, incomplete untranslated regions (UTRs) and missed exons. Compared with the previous gene models, the revised transcripts show clearer sequence motifs near splicing junctions and the end of UTRs, as well as cleaner patterns of exon–intron distribution for expression tags and cross-species conservation scores. Strikingly, 1292 exon–intron boundary revisions between coding exons corrected the previously mis-annotated open reading frames. The revised gene models were experimentally verified in randomly selected cases. We further integrated functional genomics annotations from 〉60 categories of public and in-house resources and developed an online accessible database. User-friendly interfaces were developed to update, retrieve, visualize and download the RhesusBase meta-data, providing a ‘one-stop’ resource for the monkey research community.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    TCMID: traditional Chinese medicine integrative database for herb molecular mechanism analysis (2012)
    Oxford University Press
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    Publication Date: 2012-12-20
    Description: As an alternative to modern western medicine, Traditional Chinese Medicine (TCM) is receiving increasingly attention worldwide. Great efforts have been paid to TCM’s modernization, which tries to bridge the gap between TCM and modern western medicine. As TCM and modern western medicine share a common aspect at molecular level that the compound(s) perturb human’s dysfunction network and restore human normal physiological condition, the relationship between compounds (in herb, refer to ingredients) and their targets (proteins) should be the key factor to connect TCM and modern medicine. Accordingly, we construct this Traditional Chinese Medicine Integrated Database (TCMID, http://www.megabionet.org/tcmid/ ), which records TCM-related information collected from different resources and through text-mining method. To enlarge the scope of the TCMID, the data have been linked to common drug and disease databases, including Drugbank, OMIM and PubChem. Currently, our TCMID contains ~47 000 prescriptions, 8159 herbs, 25 210 compounds, 6828 drugs, 3791 diseases and 17 521 related targets, which is the largest data set for related field. Our web-based software displays a network for integrative relationships between herbs and their treated diseases, the active ingredients and their targets, which will facilitate the study of combination therapy and understanding of the underlying mechanisms for TCM at molecular level.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 5
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    The hOGG1 Ser326Cys polymorphism contributes to cancer susceptibility: evidence from 83 case-control studies (2012)
    Oxford University Press
    Details
    Publication Date: 2012-04-25
    Description: The Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase ( hOGG1 ) gene had been implicated in cancer susceptibility. Studies investigating the associations between the Ser326Cys polymorphism and cancer susceptibility showed conflicting results. To derive a more precise estimation of the relationship, a meta-analysis was performed. This meta-analysis was performed from 83 case–control studies, including 27 918 cases and 33 399 controls. The fixed and random effect models were used to estimate the odds ratios (ORs) and their 95% confidence interval (CI) for various contrasts of this polymorphism. The combined results based on all studies showed that the hOGG1 Ser326Cys polymorphism was associated with an increased cancer susceptibility in different genetic models. In the stratified analyses, the association was significantly in head and neck cancer (homozygote comparison: OR = 2.19, 95% CI: 1.20–4.01, P heterogeneity = 0.002; heterozygote comparison: OR = 1.48, 95% CI: 1.11–1.99, P heterogeneity = 0.004; dominant model comparison: OR = 1.58, 95% CI: 1.14–2.19, P heterogeneity 〈 0.001; recessive model comparison: OR = 1.73, 95% CI: 1.02–2.94, P heterogeneity = 0.002; and additive model comparison: OR = 1.43, 95% CI: 1.09–1.88, P heterogeneity 〈 0.001) which remained for studies of the Asian populations and hospital-based of control sources. But it was not observed in other cancer types of the European population and population based of control sources. This meta-analysis suggested that the hOGG1 Ser326Cys polymorphism might contribute to an increased risk on cancer susceptibility. More studies based on larger sample size should be performed to confirm the findings.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    EGFR 3'UTR 774T〉C polymorphism contributes to bladder cancer risk (2012)
    Oxford University Press
    Details
    Publication Date: 2012-12-20
    Description: Much evidence show that over-expression of epidermal growth factor receptor (EGFR) plays an important role in regulating carcinogenesis. Genetic variations in 3' untranslated region (3'UTR) of gene have been reported to affect gene expression by interfering with microRNAs (miRNAs), which are thought to function as either tumour suppressors or oncogenes by binding to their target mRNA. In this study, we investigated the association between the EGFR 3'UTR 774T〉C polymorphism and bladder cancer risk. We used the TaqMan technology to genotype this genetic variant in a hospital-based case–control study of 908 bladder cancer patients and 1239 controls in a Chinese population. We found that the 774CC genotype was associated with a statistically significantly increased risk of bladder cancer [adjusted odds ratio = 1.29, 95% confidence interval = 1.05–1.58], compared with the 774TT/TC genotype, and this increased risk was more pronounced among subgroups of age 〉 65 years, non-smokers and patients’ tumour invasive stage. Furthermore, luciferase assays in T24 cell showed that EGFR 3'UTR 774 T to C substitution could increase the expression of EGFR, which was consistent with the association study finding. Additionally, we also provide evidence that 774T〉C polymorphism increasing EGFR expression was not regulated by hsa-miR-214 binding. These findings suggested that EGFR 3'UTR 774T〉C polymorphism may contribute to susceptibility to bladder cancer.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Problems involved in the shell-side performance of a longitudinal-flow shell-and-tube heat exchanger with decrease in L/D and its solutions (2012)
    Oxford University Press
    Details
    Publication Date: 2012-11-09
    Description: This paper presents a numerical simulation of the fluid flow and heat transfer in the shell-side of a large-scale shell-and-tube heat exchanger with longitudinal flow through porous-medium and distributed-resistance model. Such characteristics as flow field distribution, shell-side pressure drop, heat transfer performance and overall performance factor of the shell-side were studied with change in L / D and Re . It was shown that when L / D decreased from 6.0 to 1.5 with the same Re , the fluid flow maldistribution became intense, pressure drop increased sharply, and that the overall performance factor decreased sharply. Particularly, when L / D ≤ 2.0, the problems became more and more serious. Through a detailed analysis of the pressure field distribution, it was discovered that 〉80% of the total pressure drop occurred in the region of the inlet and the outlet, where the fluid flow mainly cross the tube bundle. In order to solve the problems, the use of a novel structure of multi-parallel-channel inlet and outlet (MPC) in the shell-side was proposed. A comprehensive investigation showed that MPC is very effective not only in optimizing the fluid flow distribution of the shell-side and enhancing the global heat transfer performance of a heat exchanger, but also in decreasing shell-side pressure drop.
    Print ISSN: 1748-1317
    Electronic ISSN: 1748-1325
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Published by Oxford University Press
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  • 8
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    Ancestral haplotype-based association mapping with generalized linear mixed models accounting for stratification (2012)
    Oxford University Press
    Details
    Publication Date: 2012-09-30
    Description: Motivation: In many situations, genome-wide association studies are performed in populations presenting stratification. Mixed models including a kinship matrix accounting for genetic relatedness among individuals have been shown to correct for population and/or family structure. Here we extend this methodology to generalized linear mixed models which properly model data under various distributions. In addition we perform association with ancestral haplotypes inferred using a hidden Markov model. Results: The method was shown to properly account for stratification under various simulated scenari presenting population and/or family structure. Use of ancestral haplotypes resulted in higher power than SNPs on simulated datasets. Application to real data demonstrates the usefulness of the developed model. Full analysis of a dataset with 4600 individuals and 500 000 SNPs was performed in 2 h 36 min and required 2.28 Gb of RAM. Availability: The software GLASCOW can be freely downloaded from www.giga.ulg.ac.be/jcms/prod_381171/software . Contact: francois.guillaume@jouy.inra.fr Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 9
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    Effects of mowing and nitrogen addition on soil respiration in three patches in an oldfield grassland in Inner Mongolia (2012)
    Oxford University Press
    Details
    Publication Date: 2012-04-13
    Description: Aims Vegetation type is important in determining variations in soil carbon (C) efflux under grassland managements. This study was conducted to examine the effects of mowing and nitrogen (N) addition on soil respiration and their dependences upon vegetation types in an oldfield grassland of northern China. Methods Soil respiration, temperature, moisture and aboveground net primary productivity (ANPP) and belowground net primary productivity (BNPP) were examined in response to mowing and N addition among the three patches dominated by different species (named as grass, forb and mixed patches, respectively) in the growing seasons (May–October) from 2006 to 2008. Important Findings Across the 3 years, soil respiration in the grass patch was greater than those in the forb and mixed patches, which could have been ascribed to the higher soil moisture (SM) in the grass patch. Mowing had no impact on soil respiration due to unaltered SM and plant growth. Soil respiration was stimulated by 6.53% under N addition, and the enhancement was statistically significant in 2006 but not in 2007 or 2008 because of the limited water availability in the later 2 years. There were no interactive effects between mowing and N addition on soil respiration. Soil respiration showed positive dependence upon SM, ANPP and BNPP across plots. The results suggest that soil water availability and plant growth could be the primary factors in controlling the temporal and spatial variations in soil respiration and its response to different treatments. Our observations indicate that grassland managements (i.e. mowing for hay once a year) may have little influence on soil respiration of the oldfield grassland in northern China.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    A highly efficient and effective motif discovery method for ChIP-seq/ChIP-chip data using positional information (2012)
    Oxford University Press
    Details
    Publication Date: 2012-04-15
    Description: Identification of DNA motifs from ChIP-seq/ChIP-chip [chromatin immunoprecipitation (ChIP)] data is a powerful method for understanding the transcriptional regulatory network. However, most established methods are designed for small sample sizes and are inefficient for ChIP data. Here we propose a new k- mer occurrence model to reflect the fact that functional DNA k -mers often cluster around ChIP peak summits. With this model, we introduced a new measure to discover functional k- mers. Using simulation, we demonstrated that our method is more robust against noises in ChIP data than available methods. A novel word clustering method is also implemented to group similar k -mers into position weight matrices (PWMs). Our method was applied to a diverse set of ChIP experiments to demonstrate its high sensitivity and specificity. Importantly, our method is much faster than several other methods for large sample sizes. Thus, we have developed an efficient and effective motif discovery method for ChIP experiments.
    Keywords: Massively Parallel (Deep) Sequencing, Chromatin and Epigenetics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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